Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health
Assessment of annexin A5 and annexin A2 levels as biomarkers for pre-eclampsia: A pilot study
Introduction
Pre-eclampsia (PE) is a multifactorial disease affecting 2–8% of pregnancies and remains a leading cause for maternal and perinatal morbidity and mortality worldwide [1]. The exact mechanisms, which lead to PE, are not clear but several factors appear to help predict who will develop this disease. These factors include family history, age and parity. The primary established pathophysiology in PE resides in the abnormal trophoblastic implantation with reduced placental perfusion. The secondary pathology appears to be endothelial cell injury, oxidative stress and activation of the coagulation system [2]. Placental dysfunction has been reported to play a major role in the pathogenesis of PE as well as modulate the disease outcome. Fibrin deposition and microthrombi are known histopathologic alterations in placental dysfunction in preeclampsia [2], [3]. The mechanisms of these thrombotic changes are not fully understood. Most studies have focused on the clotting activities and little is known about the changes in the fibrinolytic system in pregnancies complicated with this disease [4], [5].
Annexin A5 belongs to the family of annexins, which are highly homologous phospholipid binding proteins. It can be found in various cell types such as platelets and endothelial cells and has also been detected in placental villi [6]. It is an anionic phospholipid-binding protein with potent anticoagulant activity. It inhibits prothrombin activation and is able to prevent thrombus formation under normal venous and arterial blood flow conditions [7]. Several studies have suggested that annexin A5 may protect the syncytial surface against clot formation [8], [9] and lower amounts of annexin A5 expression on trophoblasts has been noted in pre-eclamptic patients compared to healthy pregnant [10], [11], [12].
Annexin A2, a member of annexin family, is a calcium-regulated phospholipid binding protein which is expressed on a number of cell types including endothelial cells, macrophages, a variety of tumor cells, and also on the brush-border membrane of placental syncytiotrophoblast [13], [14]. It is a cell surface co-receptor for plasminogen and its activator; tPA and its binding promotes significantly cell surface plasmin generation [15]. In peripheral maternal blood, there was an association between low levels of annexin A2 and PE and low fetal birth weight. Levels of expression of annexin A2 were inversely correlated with the severity of placental thrombin generation [5].
Few studies have investigated the role of annexin A5 [11], [12], [16] and annexin A2 [5], [17] in pre-eclampsia. These studies have either explored one or the other. Moreover; they mostly focused on the local expression of these proteins in the placenta tissue rather than examining blood levels of these proteins. In the current study, the role of serum annexins A5 & A2 as biomarkers of PE is carefully examined.
Section snippets
Patients’ recruitment and classification
This pilot study examined a total of 80 women; 40 were healthy pregnant women with an average age of 27 years (range:19–37) and 40 women diagnosed with pre-eclampsia (after 20 weeks of gestation) with an average age of 28 years (range:18–43). The patients were selected from the outpatient clinic of Obstetric and Gynecological Department in Mansoura University Hospital. Clinical characteristics of the study population are shown in Table 1. Diagnosis of pre-eclampsia and determination of severity
Results
The clinical characteristics of patients’ groups compared with controls are summarized in Table 1. The patients’ ages ranged from 18–43 years compared with an age-matched control group (ages ranged from 19–37 years). There were no significant differences in maternal age, gravidity and parity between total patients and controls. There were significant differences in mean gestational age between total patients and controls and between each of the mild and severe PE in comparison with control group (
Discussion
Dysfunction of the placenta has been considered to play an important role in the pathogenesis of PE as well as in the prognosis of the disease. One of the most common histopathologic dysfunctional alterations seen in the placenta of PE patients are various grades of thrombosis and placental infarctions [3], [4], but the mechanism behind these microthrombi is not fully understood [5]. While several factors such as family history, age and parity appear to help predict who will develop the
Conclusion
Based on the data presented in this study, annexin A2 can potentially predict the development of pre-eclampsia. The low annexin A2 levels (<0.89 ng/ml) together with higher blood pressure and proteinuria constitute a higher risk to develop pre-eclampsia. However, the relatively small number of patients limit a validated generalizable conclusion. Further studies with larger sample size need to be conducted to prove/ improve the utility of annexin A2 as predictor/ biomarker for pre-eclampsia.
Author contributions
Marwa Abd El-Latif & Hanan Azzam: designed and conducted research, analyzed data and drafted manuscript. Osama Warda recruited patients and provided clinical data. Solafa El-Sharawy & Hayam Ghoneim designed and supervised research. Maha Othman contributed intellectually to the study and wrote manuscript.
Conflict of interest
The authors have no competing interests to declare.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
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